This invention relates to the synthesis of carbapenem intermediates. The invention is particularly useful in that it facilitates the presence of a .beta.-methyl group upon cyclization to form the non-beta lactam ring of the carbapenem nucleus.
The side chain which is attached at position two of the carbapenem nucleus can be introduced prior to non-beta lactam ring cyclization. This reduces the number of steps which are necessary to produce the final compound. The side chain can be in protected or unprotected form, or a precursor of the side chain can be used, such as a coupling moiety, which can be present in protected or unprotected form prior to cyclization. This facilitates the addition of the side chain. Thus, the process described herein has extended utility, in that many different carbapenem antibiotics can be synthesized.
Prior syntheses of carbapenems have relied upon the very time consuming Mitsunobu reactions to synthesize the carbapenem framework. This invention responds to the need for a more convergent and facile procedure for synthesis of these compounds.